title: The contribution of plukenetione A to the anti-tumoral activity of Cuban propolis.
abstract: Increasing efforts are directed toward finding applications for natural products and their derivatives in the treatment of human diseases. Among such products, propolis, a resinous substance produced by honey bees from various plant sources, has been found to be a promising source of potential therapeutics. In the present work, we aimed at studying the perspective of Cuban propolis as a source of possible anti-cancer agents. We found an anti-metastatic effect in mice and considerable cytotoxicity without cross-resistance in both wild-type and chemoresistant human tumor cell lines. Plukenetione A--identified for the first time in Cuban propolis--induced G0/G1 arrest and DNA fragmentation in colon carcinoma cells. Furthermore, the activities of both topoisomerase I and DNA polymerase were inhibited, while the expression of topoisomerase II-beta, EGF receptor, and multidrug resistance-related protein genes was found repressed. We assume that plukenetione A contributes to the anti-tumoral effect of Cuban propolis mainly by targeting topoisomerase I as well as DNA polymerase.
authors.affiliation: Division of Clinical Pharmacology, Ruhr-University of Bochum, Universitaetsstr. 150, D-44801 Bochum, Germany. david.diaz-carballo@rub.de
authors.forename: David
authors.initials: D
authors.lastname: Díaz-Carballo
authors.forename: Sascha
authors.initials: S
authors.lastname: Malak
authors.forename: Walter
authors.initials: W
authors.lastname: Bardenheuer
authors.forename: Michael
authors.initials: M
authors.lastname: Freistuehler
authors.forename: H
authors.initials: H
authors.lastname: Peter Reusch
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002851:Chromatography, High Pressure Liquid; D003462:Cuba; D004249:DNA Damage / Q000187:drug effects; D004258:DNA Polymerase III / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000235:genetics / Q000378:metabolism; D005260:Female; D016193:G1 Phase / Q000187:drug effects; D020869:Gene Expression Profiling; D006801:Humans; D020128:Inhibitory Concentration 50; D051379:Mice; D011083:Polycyclic Compounds / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D011429:Propolis / Q000737:chemistry* / Q000494:pharmacology; D016192:Resting Phase, Cell Cycle / Q000187:drug effects; D059004:Topoisomerase I Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D011083:Polycyclic Compounds; D059004:Topoisomerase I Inhibitors; C534123:plukenetione A; D011429:Propolis; C065639:DNA polymerase A; D004258:DNA Polymerase III; D004264:DNA Topoisomerases, Type I